刘煜昊
阜外华中心血管病医院 心血管内科
BACKGROUND:Registry-based studies of pediatric pulmonary arterial hypertension (PPAH) are scarce in developing countries, including China. The PPAH risk assessment tool needs further evaluation and improvement.RESEARCH QUESTION:What are the characteristics and long-term survival of PPAH in China and what is the performance of the PPAH risk model in Chinese patients?STUDY DESIGN AND METHODS:Patients with PAH were enrolled in the national prospective multicenter registry from August 2009 through December 2019. Children 3 months to 18 years of age at the time of PAH diagnosis were analyzed.RESULTS:A total of 247 children with PAH were enrolled. The median patient age was 14.8 years, and 58.3% of patients were female. Most patients had a diagnosis of PAH associated with congenital heart disease (CHD; 61.5%) and idiopathic or heritable PAH (37.7%). The median time from symptom onset to PAH diagnosis was 24 months. The mean pulmonary artery pressure and pulmonary vascular resistance index were 70.78 ± 19.80 mm Hg and 21.82 ± 11.18 Wood Units·m2, respectively. Patients with CHD-associated PAH experienced a longer diagnostic delay and demonstrated higher pulmonary artery pressure, but better cardiac performance, than those with idiopathic or heritable PAH. An increased number of patients received targeted therapy at the last follow-up compared with baseline. The 5- and 10-year survival rates of the entire cohort were 74.9% and 55.7%, respectively, with better survival in patients with CHD-associated PAH than in those with idiopathic or heritable PAH. Patients with low risk had better survival than those with high risk according to the simplified noninvasive risk score model with weight, function class, and echocardiographic right ventricular size, both at baseline and follow-up.INTERPRETATION:Patients with PPAH in China showed severely compromised hemodynamics with marked diagnostic delay. The long-term survival of PPAH is poor despite the increased usefulness of targeted drugs. The simplified noninvasive risk model demonstrated good performance for predicting survival in Chinese children with PAH.TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT01417338; URL: www.CLINICALTRIALS:gov.
Chest 2023
BACKGROUND:The purpose of this registry was to provide insights into the characteristics, treatments and survival of patients with PAH-CHD in China.METHODS:Patients diagnosed with PAH-CHD were enrolled in this national multicenter prospective registry. Baseline and follow-up data on clinical characteristics, PAH-targeted treatments and survival were collected.RESULTS:A total of 1060 PAH-CHD patients (mean age 31 years; 67.9% females) were included, with Eisenmenger syndrome (51.5%) being the most common form and atrial septal defects (37.3%) comprising the most frequent underlying defect. Approximately 33.0% of the patients were in World Health Organization functional class III to IV. The overall mean pulmonary arterial pressure and pulmonary vascular resistance were 67.1 (20.1) mm Hg and 1112.4 (705.9) dyn/s/cm5, respectively. PAH-targeted therapy was utilized in 826 patients (77.9%), and 203 patients (19.1%) received combination therapy. The estimated 1-, 3-, 5-, and 10-year survival rates of the overall cohort were 96.9%, 92.9%, 87.6% and 73.0%, respectively. Patients received combination therapy had significantly better survival than those with monotherapy (p = 0.016). NT-proBNP >1400 pg/ml, SvO2 ≤ 65% and Borg dyspnea index ≥ 3 and PAH-targeted therapy were independent predictors of mortality. Hemoglobin > 160g/L was a unique predictor for mortality in Eisenmenger syndrome.CONCLUSIONS:Chinese PAH-CHD patients predominantly exhibit Eisenmenger syndrome and have significantly impaired exercise tolerance and right ventricular function at diagnosis, which are closely associated with long-term survival. PAH-targeted therapy including combination therapy showed a favorable effect on survival in PAH-CHD. The long-term survival of Chinese CHD-PAH patients remains to be improved.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2023
OBJECTIVE:To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI).METHODS:This retrospective study included 81 patients who underwent transcatheter closure for postinfarction VSR. We analyzed clinical data from hospitalization and the 30-day follow-up, compared clinical data from the survival and death groups, and explored the best closure time and the safety and efficacy of occlusion. The risk factors for death at 30 days were analyzed by logistic regression.RESULTS:C-reactive protein (CRP), white blood cell counts, N-terminal pro brain natriuretic peptide (NT-ProBNP), and aspartate aminotransferase were higher in the death group than in the survival group (p < .01), with a higher rate of application of vasoactive drugs, and a shorter time from AMI to operation (p < .05). At 30 days postocclusion, 19 patients (23.5%) had died. The mortality rate was significantly lower for operation performed 3 weeks after AMI than for operation performed within 3 weeks of AMI (12.5% vs. 48%, p < .001). Devices were successfully implanted in 76 patients, with 16 (21.1%) operation-related complications and 12 (15.8%) valve injuries. Cardiac function improved significantly (p < .001) at discharge (N = 66) and 30 days after procedure (N = 62). Qp/Qs and pulmonary artery systolic pressure decreased significantly, while aortic systolic pressure increased significantly (p < .001). Additionally, EF and LVDd improved (p < .05) after occlusion. Increases in CRP and NT-ProBNP were risk factors for death at 30 days after closure (p < .05).CONCLUSION:Percutaneous VSR closure can be a valuable treatment option for suitable patients with VSR.
Clinical cardiology 2023
BACKGROUND AND OBJECTIVE:Nationally representative reports on the characteristics and long-term survival of pulmonary arterial hypertension (PAH) from developing countries are scarce. The applicability of the current main risk stratifications and the longitudinal changes in goal-oriented treatments have yet to be elucidated in real-world settings. Therefore, we aimed to provide insights into the characteristics, goal-oriented treatments and survival of PAH in China and to explore the applicability of the main risk stratifications in our independent cohort.METHODS:PAH patients were consecutively enrolled from a national prospective multicentre registry. Data on baseline, follow-up re-evaluation and therapeutic changes were collected.RESULTS:A total of 2031 patients were enrolled, with congenital heart disease (CHD)-PAH (45.2%) being the most common aetiology. The mean age was 35 ± 12 years, and 76.2% were females. At baseline, approximately 20% of the patients with intermediate or high risk received combination treatment. At follow-up, approximately half of the re-evaluated patients did not achieve low-risk profiles, and even among patients who received combination therapy at baseline, 4% of them still worsened. The rate of combination therapy increased significantly from 6.7% before 2015 to 35.5% thereafter. The main risk assessment tools demonstrated good performance for predicting survival both at baseline and at follow-up.CONCLUSION:Chinese PAH patients show both similar and distinct features compared to other countries. Current main risk stratifications can significantly discriminate patients at different risk levels. There were still many patients not achieving low-risk profiles at follow-up, indicating more aggressive treatment should be implemented to optimize the goal-oriented treatment strategy.
Respirology (Carlton, Vic.) 2022
Objective:This study is aimed at comparing cardiac computed tomographic angiography (CTA) with echocardiography in the assessment of ventricular septal perforation diameter.Methods:A total of 44 ventricular septal rupture (VSR) patients undertaking transcatheter occlusion were included and randomly divided into the CTA group and echocardiography group with a 1 : 1 ratio. Clinical data, operation-related data, and 30 d follow-up data were collected and analyzed.Results:Incidence of closure failure, occluder displacement, poor occluder molding, and occluder waist diameter shrinkage between the two groups were not statistically different. The mean residual shunt volume in the echocardiography group (4.2 (3.1, 5.9) mm) was significantly higher than that in the CTA group (2.1 (0, 4.0) mm) with a p value of 0.005. However, no significant differences were found in all-cause mortality and incidence of operative complications within 30 days after surgery. Within the CTA group, the correlation was strongest between postoperative occluder diameter and long diameter measured by CTA with a correlation coefficient of 0.799 and p < 0.001, followed by the correlation between postoperative occluder diameter and mean diameter measured by CTA with a correlation coefficient of 0.740 and p < 0.001. The diameter measured by echocardiography was not correlated to postoperative occlude diameter.Conclusion:Assessment of VSR diameter by cardiac CTA is more accurate than by echocardiography.
Cardiovascular therapeutics 2022
BACKGROUND:At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients.METHODS:Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance.RESULTS:A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score).CONCLUSIONS:A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients.TRIAL REGISTRATION:ClinicalTrials.gov (Identifier: NCT01417338).
BMC pulmonary medicine 2021
BACKGROUND:Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD).METHODS:One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups.RESULTS:At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05).CONCLUSIONS:The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.
Chinese medical journal 2021
BACKGROUND AND OBJECTIVE:The purpose of this study was to report the characteristics and long-term survival of patients with CTEPH treated in three distinct ways: PEA, BPA and medical therapy.METHODS:Patients diagnosed with CTEPH were included in the registry that was set up in 18 centres from August 2009 to July 2018. The characteristics and survival of patients with CTEPH receiving the different treatments were reported. Prognostic factors were evaluated by Cox regression model.RESULTS:A total of 593 patients with CTEPH were included. Eighty-one patients were treated with PEA, 61 with BPA and 451 with drugs. The estimated survival rates at 1, 3, 5 and 8 years were, respectively, 95.2%, 84.6%, 73.4% and 66.6% in all patients; 92.6%, 89.6%, 87.5% and 80.2% in surgical patients; and 95.4%, 88.3%, 71.0% and 64.1% in medically treated patients. The estimated survival rates at 1, 3, 5 and 7 years in patients treated with BPA were 96.7%, 88.1%, 70.0% and 70.0%, respectively. For all patients, PEA was an independent predictor of survival. Other independent risk factors were CHD, cardiac index, PVR, big endothelin-1, APE and 6MWD.CONCLUSION:This is the first multicentre prospective registry reporting baseline characteristics and estimated survival of patients with CTEPH in China. The long-term survival rates are similar to those of patients in the international and Spanish registries. PEA is an independent predictor of survival.
Respirology (Carlton, Vic.) 2021
AIMS:Atherosclerosis (AS) is a common cardiovascular disease with complicated pathogenesis. Long non-coding RNAs (lncRNAs) have been reported to be associated with AS progression. We aimed to explore the role and underlying mechanism of HOXA transcript at the distal tip (HOTTIP) in AS.MATERIALS AND METHODS:Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HOTTIP, miR-490-3p and high mobility group B 1 (HMGB1) in AS patients' sera and oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HA-VSMCs). Cell Counting Kit-8 (CCK-8) assay and transwell assay were conducted to evaluate the proliferation and migration of HA-VSMCs, respectively. Western blot assay was carried out to determine the levels of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), MMP9 and HMGB1. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the targeting association between HOTTIP and miR-490-3p, as well as miR-490-3p and HMGB1.KEY FINDINGS:HOTTIP and HMGB1 were upregulated and miR-490-3p was downregulated in the sera of AS patients and ox-LDL-stimulated HA-VSMCs. HOTTIP knockdown suppressed ox-LDL induced proliferation and migration in HA-VSMCs. MiR-490-3p was identified as a target of HOTTIP and HOTTIP overexpression abolished the inhibition on cell proliferation and migration mediated by miR-490-3p in ox-LDL-induced HA-VSMCs. Moreover, miR-490-3p inhibition promoted cell proliferation and migration by directly targeting HMGB1 in ox-LDL-induced HA-VSMCs. Besides, HOTTIP knockdown repressed the activation of PI3K-AKT signaling pathway.SIGNIFICANCE:HOTTIP knockdown suppressed cell proliferation and migration by regulating miR-490-3p/HMGB1 axis and PI3K-AKT pathway in ox-LDL-induced HA-VSMCs.
Life sciences 2020
Atherosclerosis is a common and deadly cardiovascular disease with extremely high prevalence. Areas of the vasculature exposed to oscillatory shear stress (OSS) or disturbed blood flow are particularly prone to the development of atherosclerotic lesions. In part, various mechanosensitive receptors on the surface of endothelial cells play a role in regulating the ability of the vasculature to cope with variations in blood flow patterns. However, the exact mechanisms behind flow-mediated endothelial responses remain poorly understood. Along with the development of highly specific receptor agonists, the class of G coupled-protein receptors has been receiving increasing attention as potential therapeutic targets. G coupled-protein receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA1 ), is activated by lactate, its endogenous ligand. In the present study, we show for the first time that expression of GPR81 is significantly downregulated in response to OSS in endothelial cells and that activation of GPR81 using physiologically relevant doses of lactate can rescue OSS-induced reduced GPR81 expression. Importantly, our findings demonstrate that activation of GPR81 can exert valuable atheroprotective effects in endothelial cells exposed to OSS by reducing oxidative stress and significantly downregulating the expression of inflammatory cytokines including interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and high mobility group box 1 (HMGB1). We also show that activation of GPR81 can potentially prevent the attachment of monocytes to the endothelium by suppressing OSS-induced secretion of vascular cellular adhesion molecule (VCAM)-1 and endothelial-selectin (E-selectin). Finally, we show that activation of GPR81 can rescue OSS-induced reduced expression of the key atheroprotective transcription factor Kruppel-like factor 2 (KLF2), which is mediated through the extracellular-regulated kinase 5 (ERK5) pathway. These findings demonstrate a potential protective role of GPR81 against atherogenesis and that targeted activation of GPR81 may inhibit endothelial inflammation and dysfunction induced by OSS.
IUBMB life 2019
